Over the past decade, efforts have indicated the ability to culture mononuclear cells (MCs) in three-dimensional systems. Indeed, these principles have been incorporated in the development of platforms for the evaluation of adult vaccine responses. However, thus far, published tissue engineering work has not taken into account age-dependent changes in immunity in an organism, some of which depend on differences in soluble components of human autologous plasma. The immune responses of newborns and infants are distinct and not predictable from those of adults due to differences in both their cellular and humoral (i.e., soluble) components. Neonatal leukocytes and in particular monocytes and dendritic cells, demonstrate impairments in migration, Th1-polarizing cytokine production, and antigen-presenting cell (APC)-lymphocyte interactions. Of note, the known tissue engineering systems have employed xenologous materials such as fetal bovine serum, or have employed heat-treated pooled human serum and have therefore not taken into account immunomodulatory components unique to intact autologous neonatal plasma.